Alkoxy isobutyric acid derivatives



Patented Dec. 6, 1949 ALKOXYJSQBUTYRIC AGI'D DERIVATIVES" CharlesWeizmann, London, England, assignor to; Rolymerisable Products Limited,London, Eng,- land, aliritishcompany No nrawing, Application January 9,1946,

' Serial No. 640,129:

1.1...Glaimsr The present invention hasreference to the making of:certain alkoxy-isobutyric acids and their-derivatives (e. g. esters).This application is a continuation in part of'my co-pending applicationSer. No. 470,360 filed December 28, 1942-, (now abandoned) Previouslyitwas proposed to treat chloretone (a molecular compound or condensationproduct of chloroform and acetone) with a concentrated aqueous solutionof' causticpotash and to there after *add methy-lalcoholto the productso produced; and to: then boil the mixture. Such a process was: statedto yieldmethyl methacrylate, which could lee-separated from the otherproducts present byfractional distillation. Insaid process, thechloretone and the aqueous caustic potash solution were indicated to beat room temperature when mixed together. Such a process is inoperativeto produce the result stated, since'the said'first reaction is sostrongly exothermio-thatthe-reaction is violent and a too far-goingdecomposition of the product is produced. y

In accordance with the presentinvention, the reaction'is greatlysloweddown by greatly limiting the amount of water present (ifany), usingagreat-bulk of an-aliphatic alcoholinthereaction mixture, and previouslystrongly refrigerating the alcoholic solutions before mixing the sameand regulating the temperature throughoutthe reaction. Thusthe-first'reaction can be conducted'without approaching the hightemperatures at which such side reactions (decompositions) can takeplace;

The prcsentinventionhas-:fcr. its object. he safeproduction of; certain.alkcay-isohutyric acids andithcir der vatives. esters) inyieldsapproachs ingrtheorctical;

These acids give the usualidm'ivatives, such as esters of;phenylhydrazides. The esterification, toryinstance; can becarried outwith; alcohols in the presence of sulphuric acid. Underv certainconditions, especially in the case of higher ale-0.1 hols, thispro'cess,is accompanied by a substantial conversion into; methacrylic; acidesters.

It is obviously notessential for the method thatthealkyl'groups-inlthealcohol andin the acid radical of the alkoxyisobutyric acid 'estersare oneandthesa-me.

2"; The following examples of] the formation of certain products aregiven-by way of-example:

EXAMPLE 1 a-(z-ethyl-heazoxy) -2'sobutyric acid (new..substance) Asolutionofflig; (0.4 mol) acetone-chloroformin 200 cc. 2' ethyl-hexanol'at 2 C. was slowly added to the vigorously stirred suspension o f g:(1:6 moi) pure-potassiumhydroxide-powder-in 400cc; of 2-ethyl-hexanolat4 C. The temperaturewasmaintained at 0 to 5 during such addition. Thereaction Wasvcompletedby heating on a steambath for 2 hours. Afterfiltration-of *the-KClformed; the clear filtrate was evaporated invacuoto dryness; the residual salt mixture Was'treatedwith a; slightexcess of dilute sulphuric acid. Worked up in the usual way, 61 g.a-(2-ethyl-hexoxy)-isobutyric acid, i. e. 70.5% of thetheoretical'a-mount was obtained. The acid is a colorless liquid of B.P. 141/12 mm. absolute pressure.

Analysis: from; 4:120. mg; 10,-.130 mg. CO2 and 4.130 mg. H2O,

Cale-.forGmI-IzrOs: 6.636% C, 11.2%.H.

liquidmasaleftby acidifying with an. ex.- cessqfjdilute sulphuric acid-is.- filtered, to remove most; oithcpotassium sulphate. and theliberated EXANIPLE 2 Butyl ester of e-(z-ethyl-hexoacy) -isobutyric acid(new) A solution of 100 g. a-(2-ethyl hexoxy)-isobutyric acid (made asin Example 1) in 230 cc. n-butanol, containing 2 g. tannic acid as polymerization inhibitor and 2.3 cc. conc. H2SO4, as W Analysis: 4.485 mg.:11.650 mg. co. and 4.680 mg.

Found: 70.84% c, 11.67% H Calc. for C16H32O31 70.65% C, 11.85% H EXAMPLE3 D decyl ester of e-(Z-ethyZ-herozry) -i80blLt1 /T2'c acid (newcompound) 40 g. a(2-ethyl-hexoxy) -isobutyric acid were mixed with 100g. 1-dodecyl alcohol, 1 g. conc. sulphuric acid, and 1 g. tannic acidand the mixture heated at 120 C. for 24 hours. The reaction flask wasconnected with a bent condenser so as to remove the water liberated inthe esterification. The product was neutralized with calcium carbonateat about 80 and directly fractionated. 51 g. unchanged dodecyl alcoholwere recovered in the range between 154 and .200/10 min. Then thefraction 200-260/ 10 mm. was taken and redistilled. B. P. 232/ 10 mm.Yield, 60 g.=86% f the theory. Theester solidified slightly below roomtemperature and can be recrystallized by precipitation of its acetonicsolution with al cohol. The ester is insoluble in alcohol whichdifferentiates it from dodecyl alcohol, but miscible with petroleumether-acetone mixture.

The term chloretone or acetonechloroform as used herein, is intended tocover a double compound or condensation product of chloroform andacetone, molar ratio 1:1.

The process as described herein forms the subject matter of a copendingapplication, Ser. No. 70,589, filed Jan. 12, 1949, division beingrequired by the U. S. Patent Ofiice.

, I claim:

1. A process of producing an alkali salt of an alkoxy-isobutyric acidwhich comprises bringing together, at not above 5 0., throughout saidstep, 1 mol of chloretone with about 4 mols of an alkali metalhydroxide, in the presence of more than 20 mols of an alcohol, any waterpresent being not over 8 mols, the alcohol being in amount greater thanthe sum'of all the other components of said reaction mixture, allowingthe mixture to stand at roomtemperature, and thereafter heatingsufiiciently to s-ubstantially'complete the re action.

2. A process of producing an or alkoxy-isobutyric acid whichcomprises'bringing together at not above 5 0., throughout said step,chloretone with a member of the group consisting of alkali metalhydroxides and alkali metal alcoholates, in the presence of an aliphaticalcohol in the amount of over one half of the entire reaction mixture,and thereafter allowing the reaction to continue for a time at aboutroom temperature, then heating to suiliciently complete the reaction,and. thereafter removing the solid potassium chloride formed, and actingupon the reaction holic solvent, while maintaining the temperatureproduct with a mineral acid in amount sufilcient to combine with all thealkali present, including that which is in combination with the aalkoxyisobutyric acid.

3. A process of making an 0: alkoxy isobutyric acid which comprisesmixing chloretone with an alcohol and a member of the group consistingof alkali metal hydroxides and alkali metal alcoholates, while at atemperature not substantially above 5 C., during the whole of the mixingstep, the amount of the alcohol being over three times the amount of thechloretone, thereafter heating the mixture to boiling, removing solidpotassium chloride formed and removing the excess of alcohol, acidifyingthe reaction product and separating the u alkoxy isobutyric acid fromthe acidified product.

4. A process which comprises mixing an icecold solution of chloretoneand an ice-cold solution of potassium hydroxide in an organic alco- 7during the whole of the said mixing step at a temperature notsubstantially above 5 C., and

thereafter heating the mixture to sufiiciently complete the reaction.

5. A process as claimed in claim 4 in which the H solvent is ethyleneglycol monobutyl ether.

' about room temperature for a substantial period of time, thenrefluxing the mixture for a substantial period of time, then removingthe solid alkali metal chloride from the mixture, acidifying themixture, and separating the on alkoxy isobutyric acid from the acidifiedproduct.

'7. A process of making an a alkoxy isobutyric acid which comprisesadding a solution of chloretone in an aliphatic alcohol to a solution ofan alkali metal hydroxide in an aliphatic alcohol,

. the ratio of alcohol to chloretone being over 35:1 by weight, all ofsuch addition being made while the reaction mixture isat about 0 C.,thereafter boiling the mixture for suificiently completing the reaction,acidifying the reaction mixture and separating the a alkoxy isobutyricacid therefrom.

8. A process which comprises mixing together solutions of chloretone andof a member of the group consisting of alkali metal hydroxides andalkali metal alcoholates, both dissolved in 2- ethyl-hexanol, andmaintaining the reaction mixture at not above 5 C. during the whole ofsuch mixing step, and thereafter heating'the mixture sufficiently tosubstantiallycomplete the reaction, and separating solid alkali chloridefrom the reaction product.

9. A process which comprises mixing'solutions of chloretone and of amember of the group consisting of alkali metal hydroxides and alkalimetal alcoholates, in an excess of an alcohol containing an ethyleniclinkage, and during the whole of said mixing step keeping the reactionmixture at a temperature not substantially above 5 C., thereafterallowing the mixture to stand at room temperature for several hours,separating solid alkali chloride from the reaction mixture,

and thereafter acidifying the reaction mixture with a mineral acid.

10. A process which comprises mixing solutions of chloretone and of amember of the group con sisting of alkali metal hydroxides and alkalimetal alcoholates, in an ethylene glycol monoalkyl ether, andmaintaining the solution at a temperature not substantially above 5 C.,during all of such mixing step, and thereafter heating the reactionmixture to about 100 C. until the reaction is sufficiently completed,removing the solid alkali chloride from the reaction mixture andtreating the rest of the reaction mixture with a dilute mineral acid.

11. As a new product, u-(2-ethyl-hexoxy) -lsobutyric acid, this being acolorless liquid boilin at about 141 C. under 12 mm. absolute pressure.

CHARLES WEIZMANN.

6 REFERENCES crrEn The following references are of record in the file ofthis patent:

UNITED STATES PATENTS OTHER REFERENCES Hell et a1., "Ber. Deut. Chem.,vol. 10, 449 (1877).

15 Polstorfi et al., Berichte (Deutsch. Chem.

Gesel1.), Vol. 45, pp. 1905-1912 (1912).

Banti, Gazz. Chim. Ital., vol. 59, pp. 819-824 (1929).

Certificate of Correction Patent No. 2,490,109 December 6, 1949 CHARLESW'EIZMANN It is hereby certified that errors appear in the printedspecification of the above numbered patent requiring correction asfollows:

Column 3, line 52, beginning With 1. A process of producing strike outall to and including the Words and period dilute mineral acid. in column5, line 14, comprising claims 1 to 10 inclusive; same column 5, line 15,strike out the numeral and period 11. before the remaining claim; in theheading to the printed specification, line 8, for 11 Claims read 1Claim; and that the said Letters Patent should be read with thesecorrections therein that the same may conform to the record of the casein the Patent Ofiice.

Signed and sealed this 14th day of February, A. D. 1950.

THOMAS F. MURPHY,

Assistant Commissioner of Patents.

